Epitopes described in "MHC class I/peptide stability: implications for immunodominance, in vitro proliferation, and diversity of responding CTL."

Article Authors:D H Busch; E G Pamer
Article Title:MHC class I/peptide stability: implications for immunodominance, in vitro proliferation, and diversity of responding CTL.
Reference Detail
Reference ID:1000439
Abstract:Infection of BALB/c mice with Listeria monocytogenes primes CD8+ cytotoxic T cells specific for four different H2-Kd-restricted peptides. In vitro restimulation of L. monocytogenes immune splenocytes with each of these peptides resulted in larger T cell responses to p60 217-225 and mpl 84-92 than to LLO 91-99 and p60 449-457. Direct frequency analyses of immune splenocytes, however, revealed that LLO 91-99 and p60 217-225 elicit dominant T cell responses, while p60 449-457 and mpl 84-92 elicit minor, subdominant responses. Restimulation of immune splenocytes with a range of peptide concentrations revealed that T cells with dominant specificities respond optimally to low peptide concentrations, while T cells specific for subdominant epitopes expand maximally to high peptide concentrations. This disparity correlates with the stability of H2-Kd/epitope complexes: the two dominant epitopes form stable complexes, while the subdominant epitopes form less stable complexes with H2-Kd. Interestingly, T cells specific for LLO 91-99 and p60 217-225 express more complex TCR-Vbeta repertoires than p60 449-457- and mpl 84-92-specific T cells. Thus, in our system, dominant T cell responses have relatively diverse TCR repertoires and are specific for peptides that form stable complexes with MHC class I molecules. Determining the precise roles of epitope/MHC class I stability and TCR repertoire in the generation of dominant T cell responses will require further investigation.
Affiliations:Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520, USA.
Reference Type:Literature
PubMed ID:9574549
Journal:J Immunol
Journal Volume:160
Article Pages:4441-8
Journal ISSN:0022-1767
Article Chemical List:Histocompatibility Antigens Class I;Peptides;Receptors, Antigen, T-Cell
Article MeSH List:Animals; Antigen Presentation; CD8-Positive T-Lymphocytes(immunology); Cytotoxicity, Immunologic; Histocompatibility Antigens Class I(chemistry; immunology); Listeria monocytogenes(immunology); Listeriosis(immunology); Mice; Mice, Inbred BALB C; Peptides(chemistry; immunology); Receptors, Antigen, T-Cell(immunology)
Curation Last Updated:2014-10-03 19:50:09